World Hepatitis Day: a call for increased international commitment in the fight against hepatitis
The motto of this year's World Hepatitis Day, proclaimed annually on 28 July by the World Health Organisation (WHO), is “It's time to act". Hundreds of millions of people worldwide are affected by chronic viral hepatitis, which can lead to severe liver disease and cancer. The five main types of hepatitis viruses infecting humans—A, B, C, D and E—together are responsible for 1.3 million deaths and 2.2 million new infections per year. Of these, the hepatitis B virus causes most cases of persistent infections and deaths.
The German Center for Infection Research (DZIF) is involved in developing measures to improve the prevention, diagnosis and treatment of viral hepatitis with a dedicated research area. The research efforts aim to save lives, improve the health of those affected and achieve the WHO goal to significantly reduce the disease burden by 2030. Below we present some projects from the DZIF Hepatitis research area and provide links to videos on the topic provided by DZIF experts as part of a hepatitis awareness campaign.
Development of the active agent bulevirtide against hepatitis D
Over 12 million humans worldwide suffer from a chronic infection with the hepatitis D virus. This most serious viral liver disease is associated with a high risk of dying from liver cirrhosis and liver cancer. It is caused by the hepatitis D virus, which uses the surface proteins of the hepatitis B virus as a vehicle to specifically enter the cells via a protein in the membrane of liver cells—the bile salt transporter protein NTCP. A peptide that binds NTCP can prevent the virus from entering the cells. Under the name bulevirtide (brand name Hepcludex, formerly Myrcludex B), the peptide has been approved as a drug for chronic HDV infections since 2023. The development of bulevirtide is the result of a successful long-term collaboration between academic research under the leadership of DZIF scientist Prof. Stephan Urban and the pharmaceutical company MYR GmbH, which ultimately led to the takeover and global commercialisation of Hepcludex by the pharmaceutical company Gilead Sciences. Bulevirtide proved safe and effective in the treatment of chronic hepatitis D in several clinical trials.
Press releases on the topic can be found here:
Outstanding hepatitis research: DZIF Professor receives honorary doctorate (https://www.dzif.de/en/outstanding-hepatitis-research-dzif-professor-receives-honorary-doctorate)
Mechanism of action of the hepatitis B and D virus cell entry inhibitor bulevirtide deciphered (https://www.dzif.de/en/mechanism-action-hepatitis-b-and-d-virus-cell-entry-inhibitor-bulevirtide-deciphered)
In a recent study, conducted by DZIF scientists in collaboration with Gilead Sciences and published in the Journal of Hepatology in June 2024, liver biopsies from study participants were analysed before treatment and after one year of bulevirtide therapy. The analyses, led by DZIF executive board member Prof. Maura Dandri from the University Medical Center Hamburg-Eppendorf, showed that bulevirtide significantly reduced the number of hepatitis virus-D-infected cells and the signs of liver inflammation.
Therapeutic vaccines for the treatment of chronic hepatitis B—TherVacB
Chronic infection with the hepatitis B virus can lead to liver disease and cancer and poses a serious threat to around 300 million people worldwide. Therapeutic vaccines designed to stimulate the immune system to cure the disease are a promising approach for treating chronic hepatitis B. TherVacB, a novel therapeutic vaccine developed under the leadership of DZIF scientist Prof. Ulrike Protzer at the Technical University of Munich and Helmholtz Munich, is currently in the first phase Ia clinical trial testing the safety and immunogenicity of the novel vaccine candidate in healthy volunteers. The therapeutic vaccine is ready for phase Ib/IIa clinical trials, in which the safety and efficacy of TherVacB will be tested in patients with chronic hepatitis B.
A press release on the topic can be found here: Therapeutic vaccine for chronic hepatitis B enters clinical trial (https://www.dzif.de/en/therapeutic-vaccine-chronic-hepatitis-b-enters-clinical-trial)
Antibody-based therapies for the treatment of chronic hepatitis B and D—VIR-3434
A team of DZIF researchers from Heidelberg and Hamburg-Eppendorf supported the preclinical development of VIR-3434, a monoclonal antibody discovered by Vir Biotechnology Inc. that targets the hepatitis B surface antigen in the viral envelope. In a jointly conducted preclinical study using a mouse model for co-infection with hepatitis B and D viruses, the genetically engineered monoclonal antibody was shown to reduce substantially antigen concentration and hence the amounts of circulating virus and subviral particles and to effectively prevent the spread of the virus in the liver. The mouse model was developed under the leadership of Prof. Maura Dandri at the University Medical Center Hamburg-Eppendorf. Based on these results, clinical trials with the monoclonal antibody VIR-3434 are currently being conducted.
A press release on the topic can be found here: A promising investigational therapeutic monoclonal antibody to treat chronic hepatitis B and D infections (https://www.dzif.de/en/promising-investigational-therapeutic-monoclonal-antibody-treat-chronic-hepatitis-b-and-d)
Video campaign on the risks of infection with hepatitis B and D viruses
In collaboration with the TherVacB project, the D-Solve and ICE-HBV initiatives and the German Liver Foundation, the DZIF is committed to informing the public and hepatitis B patients about the risks of hepatitis B/D co-infection. In a video campaign, our scientists explain the viral disease as well as diagnosis and treatment options in easy-to-understand language. To mark World Hepatitis Day, the first videos of the campaign will be published over the next few days on the TherVacB YouTube channel under this link: https://www.youtube.com/channel/UCsc6rMwqejsiOzsc2IqyPxw.
Wissenschaftlicher Ansprechpartner:
Prof. Dr. Stephan Urban
Heidelberg University
dzifheidelberg.HYG@med.uni-heidelberg.de
Prof. Dr. Ulrike Protzer
Technical University of Munich
Helmholtz Munich
protzer@tum.de
Prof. Dr Maura Dandri
University Medical Center Hamburg-Eppendorf
m.dandri@uke.de
Originalpublikation:
Journal of Hepatology (2024), Blocking viral entry with bulevirtide reduces the number of HDV-infected hepatocytes in human liver biopsies, DOI: 10.1016/j.jhep.2024.01.035, https://www.sciencedirect.com/science/article/pii/S0168827824001144?via%3Dihub
Weitere Informationen:
https://www.dzif.de/en/world-hepatitis-day-call-increased-international-commitment-fight-against-hepatitis Press release of the German Center for Infection Research (DZIF)
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